Analogs of amanin. Synthesis of Ile3-amaninamide and its diastereoisomeric (S)-sulfoxide.
Ile3-amaninamide (3-R) and its diastereomeric sulfoxide (3-S) are obtained by oxidation of the bicyclic thioether peptide 2 by hydrogen peroxide in acetic acid. 2 was prepared by an intramolecular Savige-Fontana reaction of the linear octapeptide tert.-butylester 4 whose N-terminal Boc-Hpi residue on treatment with TFA loses the Boc group and reacts under thioether formation with the released cysteine-SH. The concomitantly deprotected carboxyl terminus is coupled intramolecularly with the free amino group of the secocompound 5 using the MA or DCCI method, thus forming the homodetic peptide ring. Compounds 3-R and 3-S agree very well with analog samples in chiroptical behavior. Thioether 2 and sulfoxide 3-R exert 50% inhibition of RNA polymerase II (or B) from Drosophila melanogaster in 10(-6) M solution whereas Ki of 3-S is about five times higher.
D000546:Amanitins / Q000138:chemical synthesis* / Q000494:pharmacology; D000818:Animals; D004331:Drosophila melanogaster; D012319:RNA Polymerase II / Q000037:antagonists & inhibitors; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D000546:Amanitins; C033088:amaninamide, Ile(3)-; D012319:RNA Polymerase II